We are investigating the origin and the significance of the tissue-specific variation in histone variant patterns, the minor histone species, and other proteins which are tightly associated with the DNA of eukaryotes. Our goal is to elucidate the structural and functional organization of mammalian chromosomes and eventually to gain insight into the molecular mechanisms responsible for the stable, tissue-specific alterations in gene activity leading to cell differentiation and the consequences of abnormalities thereof, such as cancer. We are analyzing in detail the changes in histone variant patterns during mouse liver maturation, regeneration, carcinogenesis and polyploidization, as well as during spermatogenesis of the mouse. At the same time we are characterizing the properties of native and reconstituted histone complexes containing different variants, as well as the distribution of different histone variants and minor histone species within the genome.